MEDIATION OF TRYPANOSOMA-CRUZI INVASION BY SIALIC-ACID ON THE HOST-CELL AND TRANS-SIALIDASE ON THE TRYPANOSOME

Trypanosoma cruzi attaches and invades a large variety of mammalian cells. The nature of the cell receptors and of the corresponding parasite counter-receptors that mediate T. cruzi-host cell interaction are not known. Three sialic acid-deficient mutants of Chinese hamster ovary (CHO) cells were used to probe the role of host sialyl residues in T. cruzi infection. All three mutants supported adhesion and infection to a much lower extent than the parental CHO cells. One of the mutants, Lec2, contains sugar chains terminating in non-reducing betaGal residues, which are acceptors for sialylation by the T. cruzi transsialidase. Re-sialylation of Lec2 cells restored T. cruzi adhesion and invasion to about the same extent as wild-type cells. Digestion of wild-type cells with bacterial sialidase reduced T. cruzi interaction but after re-sialylation, the cells were almost as good as control, naturally sialylated parental cells. These results suggest that T cruzi recognizes sialyl residues on the surface of host cells during invasion. On the other hand, affinity-purified trans-sialidase blocked T. cruzi adherence and invasion of sialylated cells, and had no effect on parasite interaction with sialic acid-deficient Lec2 mutant. Furthermore, 2,3-sialyllactose, a substrate for the trans-sialidase, competitively inhibited T. cruzi invasion of sialylated parental K1 cells, but 2,6-sialyllactose, which does not react with the trans-sialidase, was without effect, as were other sugars that do not contain alpha2,3 sialyl residues. These results suggest that the trans-sialidase functions as a counter-receptor for trypomastigote binding to alpha2,3-sialyl receptors on host cells as a prelude to T. cruzi invasion.